1. Field of the Invention
The present invention is directed to methods and compositions useful in the detection of human tumor cells. More particularly, the invention is directed to antibodies, developed against either a 580 kilodalton rat or human glycoprotein antigen, as potentially valuable tumor immunodiagnostic reagents, and further, as useful reagents in the prevention of metastatic lesions.
2. Description of the Relevant Art
Breast cancer constitutes a leading cause of deaths to women in North America and Northern Europe. Although recent advances have significantly improved the rates of detection and eradication of primary breast cancers, a large percentage of breast cancer patients will develop metastatic lesions and eventually die.
The process of tumor metastasis occurs by means of a number of sequential and highly selective steps. Many of these steps require a number of complex interactions between the tumor cells and host environment, and the majority of these interactions appear to be mediated by cell surface components. To investigate the possible functional roles of certain cell surface components in the metastatic process, various researchers have correlated the expression or enzymatic activities of these components with the metastatic potential of tumor cell subline or clones. Alternatively, the surfaces of tumor cells have been modified metabolically or enzymatically and the metastatic properties of the modified cells examined.
For example, cell surface components of spontaneously metastasizing rat mammary adenocarcinoma have been previously examined for possible biochemical markers which may be associated with mammary tumor metastasis in the rat. A system which has been found to be a useful model for rat mammary tumor metastasis is the rat 13762NF mammary adenocarcinoma described in Neri et al. (1982), J. Natl. Cancer Inst., 68: 507-517. Various cell clones and lines obtained from the 13762NF system were found to differ in their abilities to spontaneously metastasize to regional lymph nodes and distant organs. Additionally, they exhibit differences in cell and tissue morphologic appearance, karyotypes, and responses to therapeutic agents.
The expression of particular cell surface glycoproteins were found to correlate with the metastatic capabilities of these cells. For example, sialoglycoproteins having molecular weights between 175,000 and 250,000 are expressed on metastases-derived cells, while the major sialoglycoproteins have molecular weights between 80,000 and 120,000 in cells derived from a primary rat tumor. A sialoglycoprotein having a molecular weight of approximately 80,000 was reduced in expression in more metastatic rat tumor cells; another glycoprotein having a molecular weight of approximately 580,000, synthesized by rat tumor cells, was increased in expresssion in the more highly metastatic rat tumor cells. However, no metastasis-associated 580 kilodalton glycoprotein has previously been identified in, or found to be associated with, human tumor cells.
The identification of human tumor-associated antigenic proteins on human tumor cell surfaces could lead to the production of antibodies which ar capable of immunodiagnosing human tumor cells. Unfortunately, many human tumor cells surface components are either poorly or non antigenic, or are also associated with various normal human tissues. Where cell surface antigens are common to both normal and tumor cells, immunodiagnostic probes directed against such antigens are unsatisfactory in that they exhibit a high number of falsely positive reactions.
Cancer immunodiagnostic probes have heretofore been imprecise in that they either detect high numbers of falsely positive reactions and/or falsely negative reactions. Accordingly, a tumor diagnostic probe exhibiting a high degree of correlation with the human cancerous state would be useful in the early diagnosis and treatment of human tumors. Additionally, an immunodiagnostic probe which correlates with metastatic tumors, would be similarly useful to the treating oncologist or surgeon.